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Biomedical subjects

H Rotman

Publications and source records attributed to H Rotman.

18 recordsLinked to original sources
PubMed1997

A randomized, double-blind, crossover comparative endoscopy study on the gastroduodenal tolerability of a highly specific cyclooxygenase-2 inhibitor, flosulide, and naproxen.

BACKGROUND: Inhibition of constitutively expressed cyclooxygenase (Cox-1) is thought to play an important role in the gastrointestinal toxicity of nonsteroidal anti-inflammatory drugs (NSAID), while their therapeutic action may be due to inhibition of the enzyme Cox-2, which is specifically expressed at sites of inflammation. NSAIDs with high affinity and specifity for Cox-2 hold the promise of maintaining efficacy without the gastrointestinal side effects of conventional NSAIDs. METHODS: We assessed the gastrointestinal tolerability of flosulide (20 mg twice a day), a highly selective Cox-2 inhibitor with that of naproxen (500 mg twice a day), which has equal affinity for Cox-1 and -2 in 19 patients with osteoarthrosis in a randomized, double blind, crossover endoscopy study. Subjects were treated for 2 weeks with a 2-week washout period. Gastroduodenal damage was primarily assessed as by Lanza (grades 0-4). RESULTS: No stomach damage was seen in 13 (68%) patients after flosulide and in 5 (37%) after naproxen (P < 0.001). Lanza scores were significantly lower after flosulide (0.58) than after naproxen (1.47) (P < 0.001; odds ratio, 84.4; 95% confidence interval, 1.45-4908). Flosulide was significantly better tolerated (P < 0.005) than naproxen. CONCLUSION: These results endorse the idea that highly selective Cox-2 inhibitors may be associated with lesser gastrointestinal side effects than conventional NSAIDs.

Adult↗
PubMed1993

Hepatitis A antibody titres after infection and immunization: implications for passive and active immunization.

Titres of antibodies against hepatitis A virus (HAV) were determined in patients, in donors, and in volunteers after active, passive, and combined immunization. Highest titres were found in recently infected persons: in 109 IgM anti-HAV positive persons, the geometric mean titre (GMT) was 15,400 mIU/ml. The GMT in 265 anti-HAV positive blood donors was 10,700 mIU/ml. The anti-HAV seroprevalence in 19,746 donors increases with age: at the age of 40 years, 50% have antibodies. Titres after active, passive, and combined immunization were studied in three groups: 51 persons received inactivated HAV vaccine at months 0, 1, and 6. The GMT after the booster was 3,400 mIU/ml at month 7. All persons produced more than 100 mIU/ml anti-HAV. Forty-nine persons received both 5 ml immunoglobulin and three vaccinations, yielding a GMT of 1,300 mIU/ml at month 7. One person in this group produced less than 100 mIU/ml anti-HAV. Forty-nine persons received 5 ml immunoglobulin intramuscularly. At day 5 the GMT was 96 mIU/ml. The estimated minimum protective level (10 mIU/ml) was reached in 3 months. Hepatitis A vaccination may supersede the use of immunoglobulin as prophylaxis for travellers to endemic areas. Passive immunization remains necessary for protection during outbreaks. The dosage regimen for passive immunization is based on old studies using preparations with unknown anti-HAV content. Concern regarding the antibody levels in immunoglobulin preparations is justified; the prevalence of HAV antibodies in developed countries continues to fall. Our results indicate that dosage regimens should be reconsidered. Dosage should be deduced logically from the anti-HAV antibody content of the immunoglobulin preparation.

Adolescent↗
PubMed1993

A double-blind comparative study of soluble aspirin and diclofenac dispersible in the control of postextraction pain after removal of impacted third molars.

The analgesic efficacy and patient acceptability of soluble aspirin and diclofenac dispersible were compared in patients with postoperative pain after removal of impacted third molars. A total of 136 patients were randomly allocated to receive soluble aspirin 600 mg tds or diclofenac dispersible 50 mg tds after extraction under local anaesthesia of impacted third molars on one side of the mouth. The medication, which was both patient and operator blind, was reversed after extraction of the contralateral third molars 3 weeks later, the patients acting as their own controls in assessing postoperative pain, pain relief, and interincisal opening. Patients receiving diclofenac dispersible recorded significantly lower pain levels; pain relief was significantly greater and the patients' assessment significantly favoured diclofenac dispersible. Interincisal opening throughout the study period was significantly increased in the diclofenac dispersible group. The surgeons' postoperative assessment of extraction sites showed no significant difference between the two treatment groups in rate of healing. Two patients reported side-effects while taking soluble aspirin, and eight while taking diclofenac dispersible, two of whom discontinued treatment.

Adolescent↗
PubMed1991

Diclofenac inhibits monocyte superoxide production ex vivo in rheumatoid arthritis.

Effects of the nonsteroidal anti-inflammatory drug, diclofenac, on stimulated monocyte superoxide production were assessed directly in vitro and following treatment of patients with rheumatoid arthritis ex vivo. Diclofenac inhibited superoxide generation provoked by serum treated zymosan (STZ) and fluoride anion (F) but not by phorbol myristate acetate (PMA) in vitro. Following patient therapy, inhibition of superoxide production occurred when STZ and PMA, but not F were used as stimuli. No changes were seen in control subjects. The contrasting profiles of inhibition seen in vitro and ex vivo suggest an indirect effect on superoxide production during clinical use of the agent. These data are consistent with the hypothesis that anti-inflammatory drugs may act in rheumatoid arthritis by inhibiting phagocyte superoxide anion production.

Adult↗
PubMed1991

Percutaneous transluminal angioplasty of proximal subclavian artery stenosis after left internal mammary to left anterior descending artery bypass surgery.

A patient is described who underwent percutaneous transluminal angioplasty, through a brachial approach, of a high grade stenosis at the proximal portion of the left subclavian artery 1.5 years after coronary artery bypass grafting including left internal mammary to left anterior descending artery anastomosis. Symptoms of class IV angina, vertebrobasilar insufficiency and occupational arm claudication that developed after bypass surgery were promptly relieved after balloon dilation. Percutaneous transluminal angioplasty of the subclavian artery can be performed safely and provides an alternative to carotid-subclavian or axillary-axillary bypass surgery for treatment of internal mammary artery graft malfunction.

Angioplasty, Balloon↗
PubMed1991

Efficacy and tolerability of diclofenac dispersible in elderly patients with osteoarthritis.

The efficacy and tolerability of a new dispersible formulation of diclofenac were evaluated in a randomized, double-blind, placebo-controlled, multi-centre study in patients aged 60 to 80 years suffering from osteoarthritis. A total of 314 elderly patients with a mean age of 68.9 years received either 50 mg diclofenac dispersible or placebo 3-times daily for a period of 4 weeks, with paracetamol being allowed as rescue analgesic for both treatment groups. The study consisted of a baseline evaluation and two follow-up visits after 14 and 28 days of treatment. The following clinical parameters were assessed: pain at rest, on movement and on local pressure; global severity of pain; effect of pain on daily activity; duration of stiffness after immobility; rescue analgesic consumption; overall opinion of the investigator on efficacy; and occurrence of adverse events. At either one or both post-treatment assessments, diclofenac dispersible was found to be significantly superior to placebo for almost all measures of efficacy (p less than or equal to 0.05). Thirty (14.4%) patients out of 208 assessed in the diclofenac group reported adverse events compared to 18 (17%) out of 106 who received placebo; therapy was discontinued prematurely due to poor tolerability in 4.8% and 5.7% of patients, respectively. The adverse events were predominantly related to the gastro-intestinal system and were mostly mild to moderate in severity. The results of this 4-week study thus demonstrate that diclofenac dispersible is not only effective in treating osteoarthritis in the elderly but also has an acceptable tolerability profile in a patient population which is especially vulnerable to adverse effects induced by non-steroidal anti-inflammatory drugs.

Administration, Oral↗
PubMed1990

Comparison of the efficacy and tolerability of diclofenac gel (Voltarol Emulgel) and felbinac gel (Traxam) in the treatment of soft tissue injuries.

In an observer-blind, randomised study, the efficacy and tolerability of two topical NSAID preparations were assessed in 384 patients with acute soft tissue injuries. The patients were allocated to receive treatment with either diclofenac gel (Voltarol Emulgel) 4 g tds or felbinac gel (Traxam) 4 g tds for three or seven days, depending on the rate of recovery. In every parameter studied (pain at rest, pain on movement, pain on local pressure, swelling, range of movement, bruising, degree of recovery, requirement for rescue analgesics, daily pain levels), diclofenac was found to be more effective at day 3 and day 7, with the single exception of bruising at day 7. Treatment differences were statistically significant in favour of diclofenac for pain at rest (p = 0.03) and bruising on day 3 (p = 0.03), and pain on pressure at day 7 (p = 0.009). The difference in favour of diclofenac in reduction of daily pain level (as recorded on diary cards) did not quite reach significance (p = 0.06). Both preparations were well tolerated, with no significant treatment-related side-effects reported.

Administration, Topical↗
PubMed1990

A clinical and biochemical assessment of a nonthiol ACE inhibitor (pentopril; CGS-13945) in active rheumatoid arthritis.

Captopril, which is a thiol containing angiotensin converting enzyme (ACE) inhibitor that has a close structural similarity to D-penicillamine, behaves as a disease modifying antirheumatic drug (DMARD) in rheumatoid arthritis (RA). In order to ascertain whether the DMARD-like properties of captopril reside in its ability to inhibit ACE or in the thiol group, we evaluated pentopril (CGS-13945) in patients with active RA. This recently synthesized drug is a nonthiol containing ACE inhibitor. Pentopril produced little clinical improvement and no biochemical improvement in a group of 15 patients with RA, many of whom were unable to tolerate it because of in-effect or side effects. A reduction in serum ACE activity and a modest fall in blood pressure suggested that the drug was exerting its pharmacological effect. Our study strengthens the argument that the therapeutic benefit of captopril in RA probably lies in its thiol group rather than in its enzyme inhibition properties, and that the thiol group may be the effective moiety in some other DMARD.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

A clinical and biochemical assessment of prinomide in patients with rheumatoid arthritis.

Prinomide (CGS-10787B), a potential disease modifying drug, was evaluated clinically and biochemically in 15 patients with active rheumatoid arthritis. The single group study design included monthly assessments of 7 clinical measures and 22 laboratory measures. Twelve patients completed 24 weeks' therapy with prinomide 1.2 g/day. All clinical variables showed improvement which consistently reached statistical significance for articular index from Week 8 (p less than 0.01), for summated change score from Week 12 (p less than 0.01) and for pain score from Week 16 (p less than 0.05). Sustained significant improvement in laboratory variables was seen by Week 2 for erythrocyte sedimentation rate and platelet count (both p less than 0.05), and by Week 4 for plasma viscosity (p less than 0.01), IgG, IgA, IgM (all p less than 0.05).

Aged↗
PubMed1987

The morphine sparing effects of diclofenac sodium following abdominal surgery.

A randomised, double-blind placebo controlled study was undertaken to assess the analgesic efficacy of diclofenac. Following major abdominal surgery and 12 hours later, patients received either placebo or diclofenac 75 mg intramuscularly and their cumulative morphine requirements administered by a patient-controlled system over 24 hours were compared. Pain scores were also measured. Arterial blood gases and coagulation studies were assessed pre- and postoperatively. Morphine consumption was significantly greater in the placebo group (59.5 compared to 38.5 mg, p less than 0.01). Pain scores were significantly lower in the diclofenac group at 4 hours, but not thereafter. Arterial carbon dioxide was significantly increased in the control groups. There was no significant change in platelet count within each group, but a significant difference between the groups (p less than 0.05).

Abdomen↗
PubMed1982

An index of risk for obstructive airways disease.

Predictors of obstructive airways disease (OAD) have been identified, and models for estimating risk of developing OAD have been derived for the adult population of Tecumseh. Men and women 16 to 64 yr of age when first studied were reexamined after an average interval of 15 yr. Incidence rates of OAD increased with age and were higher in men than in women more than 45 yr of age. Incidence rates were significantly higher in men and women with low degrees of lung function initially, and in cigarette smokers, especially those who continued to smoke. Other risk factors included a physician's diagnosis of chronic bronchitis, or asthma, a history of cough, wheeze, shortness of breath, frequent upper or lower respiratory tract infections, bronchitis or pneumonia, leanness, and familial chronic bronchitis. Multiple logistic regression analyses identified combinations of risk factors that placed 70% of the male and 73% of the female incidence cases in the top 10% of the risk distribution. The excess risk of obstructive airways disease associated with cigarette smoking and reduced lung function and the benefits of stopping smoking are clearly apparent. For example, the risk of developing obstructive airways disease in the next 15 years is about 1 in 200 for a 45-yr-old male nonsmoker whose Vmax50 equals to 100% of predicted, if he doesn't take up smoking. The risk for a man of the same age who smokes 40 cigarettes a day and whose Vmax50 equals 80% of predicted is 1 in 5 or 6 if he doesn't cut down on his smoking and about 1 in 15 if he stops smoking.

Adolescent↗
PubMed1980

Resistance of red blood cell membrane to oxygen uptake.

The apparent association velocity constant (k'c) was determined before and after disruption of the red blood cell membrane in one of several ways: 1) radiation of the cells using a 137Cs source did not significantly alter k'c (95 +/- 39.3 and 118 +/- 35.5 mM-1.s-1), 2) incubation of the cells with sialidase produced no change in k'c (112 +/- 42.6 and 123 +/- 46.8 mM-1.s-1), 3) using papain for the incubation similarly produced no significant alteration in k'c (94 +/- 21.2 and 113 +/- 51.8 mM-1.s-1), 4) a radiomimetic agent p-chloromercuribenzene sulfonate likewise produced no significant alteration in k'c (128 +/- 16.3 and 122 +/- 3.5 mM-1.s-1), and 5) employing phospholipase C to disrupt the membrane k'c did not significantly change (115 +/- 15.3 and 112 +/- 8.7 mM-1.s-1). We conclude that either O2 traverses the membrane in a manner uninfluenced by the manipulations here employed, or that the membrane offers no significant resistance to the speed of O2 uptake.

Erythrocyte Membrane↗
PubMed1976

Carcinoma of the lung: results of treatment over ten years.

Mediastinal lymph node dissection in conjunction with pulmonary resection was performed on 437 patients with bronchogenic carcinoma at the University of Michigan Medical Center from 1959 to 1969. The absolute five- and ten-year survival rates for patients undergoing curative resection were 36.2 and 14.4%, respectively. The five-year survival of those without nodal metastases was 49.3%, and it was 31.1% in patients with hilar metastases only. The five-year survival of patients with mediastinal metastases who received radiation therapy was 23.1%. Of the 193 patients with squamous cell carcinoma, 43% lived five years free from disease. The five-year survival of patients undergoing resection who had no hilar lymph node metastases was 53%, and it was 47.5% in those with hilar metastases only. The five-year survival in patients with mediastinal metastases who received postoperative irradiation was 34.4%.

Adenocarcinoma↗
PubMed1976

Major pulmonary resection for bronchogenic carcinoma in the elderly.

The results of major pulmonary resection in 58 patients greater than 70 years of age were reviewed. The histological distribution and extent of nodal metastases in this age group are the same as in younger patients. The absolute five-year survival rate for the 55 patients undergoing curative resection was 30% (17 patients). It was 36% (11 patients) for those patients with squamous cell carcinoma and 22% (5 patients) for those with adenocarcinoma. The operative mortality was only 14% (8 patients). Of the 49 patients treated by lobectomy, 17 lived five years or more free of disease, whereas none of the 6 patients treated by pneumonectomy survived five years. The five-year survival rate of 30% in this series of elderly patients treated by major pulmonary resection makes resections in such patients with bronchogenic carcinoma worthwhile.

Adenocarcinoma↗
PubMed1975

Complications of pulmonary resection.

The following complications of pulmonary resection are discussed with reference to their frequency of occurrence, etiology, diagnosis, and treatment: pulmonary insufficiency, arrhythmias, residual intrapleural air spaces, prolonged air leaks, postpneumonectomy empyema, bronchopleural fistula, cardiac herniation, lobar gangrene, esophagopleural fistula, pulmonary embolism, and tumor embolism.

Arrhythmias, Cardiac↗
PubMedDate not supplied

Double-blind, multicenter evaluation of the efficacy and tolerability of diclofenac dispersible in the treatment of acute soft-tissue injuries.

In a randomized, double-blind, parallel-group, multicenter study, the efficacy and tolerability of diclofenac dispersible were compared with placebo in the treatment of acute soft-tissue injuries. Patients seen within 48 hours of a soft-tissue injury received either diclofenac dispersible 50 mg or placebo three times daily for 3 to 7 days, with paracetamol allowed as a rescue analgesic. Of a total of 253 recruited patients. 247 patients (122 in the diclofenac dispersible group and 125 in the placebo group) were eligible for tolerability assessment and 229 patients (115 diclofenac dispersible and 114 placebo) were eligible for efficacy analysis. In general, median reductions in the intensities of pain at rest, on movement, and on local pressure (as measured on 100-mm analog chromatic continuous scales) were greater with diclofenac dispersible than with placebo after treatment (differences did not reach statistical significance). At the center that recruited the largest number of patients, the initial median levels of pain at rest and on movement were considerably lower than those at the other centers. On reanalysis of the pain data without this center, a significant difference favoring diclofenac dispersible over placebo was noted for pain on movement and on local pressure (P < or = 0.044). With respect to daily assessment of pain severity, more patients in the diclofenac dispersible group had none or mild pain while fewer had moderate or severe pain during the early posttreatment days; this treatment difference versus placebo reached statistical significance on days 3 and 4 (P < or = 0.045).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗